It has been reported that the immune system undergoes changes due to various factors, inflammation, surgery, medication, age and gender. The aim of this study was to investigate therapy-dependent changes of salivary IgA among healthy subjects undergoing active orthodontic treatment. The levels of IgA were determined at the beginning, and after 1,4, 8,16 weeks and 32 weaks of active orthodontic treatment. A total of 100 healthy individuals (aged 15-42 years) were enrolled in the study. Two milliliters of saliva were collected from all participants, and salivary IgA levels were measured by the ELISA technique. Mean salivary IgA levels were significantly higher in subjects after 1 week as compared to subjects at the beginning of orthodontic treatment (P < 0.01).. The mean levels of salivary IgA were significantly higher after 4 and 8 weeks of therapy than those observed in the control group (P < 0.00001 and P < 0.05, respectively) and reached the highest level at 16 weeks and then remained stable during treatment. Gender had no effect on the salivary levels of IgA as any significant differences were observed between men and women. The results highlight the importance of the salivary defense mechanism, translated through the increase in the levels of IgA, once orthodontic treatment is started.